D. Palmeri et Mh. Halim, Importin beta can mediate the nuclear import of an arginine-rich nuclear localization signal in the absence of importin alpha, MOL CELL B, 19(2), 1999, pp. 1218-1225
The import of proteins into the nucleus is dependent on cis-acting targetin
g sequences, nuclear localization signals (NLSs), and members of the nuclea
r transport receptor (importin-beta-like) superfamily. The most extensively
characterized import pathway, often termed the classical pathway, is utili
zed by many basic-type (lysine-rich) NLSs and requires an additional compon
ent, importin alpha, to serve as a bridge between the NLS and the import re
ceptor importin beta. More recently, it has become clear that a variety of
proteins enter the nucleus via alternative import receptors and that their
NLSs bind directly to those receptors. By using the digitonin-permeabilized
cell system for protein import in vitro, we have defined the import pathwa
y for the Rex protein of human T-cell leukemia virus type 1. Interestingly,
the arginine-rich NLS of Rex uses importin beta for import but does so by
a mechanism that is importin alpha independent. Based on the ability of the
Rex NLS to inhibit the import of the lysine-rich NLS of T antigen and of b
oth NLSs to be inhibited by the domain of importin or that binds importin b
eta (the IBB domain), we infer that the Res NLS interacts with importin bet
a directly. In addition, and in keeping with other receptor-mediated nuclea
r import pathways, Rex import is dependent on the integrity of the Ran GTPa
se cycle. Based on these results, we suggest that importin beta can mediate
the nuclear import of arginine-rich NLSs directly, or lysine-rich NLSs thr
ough the action of importin alpha.